Dataset Information

MRNA and miRNA expression profile reveals the role of miR-31 overexpression in neural stem cell.

ABSTRACT: A detailed understanding of the character and differentiation mechanism of neural stem cells (NSCs) will help us to effectively utilize their transplantation to treat spinal cord injury. In previous studies, we found that compared with motor neurons (MNs), miR-31 was significantly high-expressed in NSCs and might play an important role in the proliferation of NSCs and the differentiation into MNs. To better understand the role of miR-31, we characterized the mRNA and miRNAs expression profiles in the early stage of spinal cord-derived NSCs after miR-31 overexpression. There were 35 mRNAs and 190 miRNAs differentially expressed between the miR-31 overexpression group and the control group. Compared with the control group, both the up-regulated mRNAs and miRNAs were associated with the stemness maintenance of NSCs and inhibited their differentiation, especially to MNs, whereas the down-regulated had the opposite effect. Further analysis of the inhibition of miR-31 in NSCs showed that interfering with miR-31 could increase the expression of MNs-related genes and produce MNs-like cells. All these indicated that miR-31 is a stemness maintenance gene of NSCs and has a negative regulatory role in the differentiation of NSCs into MNs. This study deepens our understanding of the role of miR-31 in NSCs, provides an effective candidate target for effectively inducing the differentiation of NSCs into MNs, and lays a foundation for the effective application of NSCs in clinic.

SUBMITTER: Li P

PROVIDER: S-EPMC7568549 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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mRNA and miRNA expression profile reveals the role of miR-31 overexpression in neural stem cell.

Li Pengfei P Gao Yuantao Y Li Xiao X Tian Feng F Wang Fei F Wang Yali Y Zhao Bichun B Zhang Ruxin R Wang Chunfang C

Scientific reports 20201016 1

A detailed understanding of the character and differentiation mechanism of neural stem cells (NSCs) will help us to effectively utilize their transplantation to treat spinal cord injury. In previous studies, we found that compared with motor neurons (MNs), miR-31 was significantly high-expressed in NSCs and might play an important role in the proliferation of NSCs and the differentiation into MNs. To better understand the role of miR-31, we characterized the mRNA and miRNAs expression profiles i ...[more]

PMID: 33067542

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Project description:Medulloblastoma (MB) is the most common malignant brain tumor in children and a leading cause of cancer-related mortality and morbidity. Several molecular sub-types of MB have been identified, suggesting they may arise from distinct cells of origin. Data from animal models indicate that some MB sub-types arise from multipotent cerebellar neural stem cells (NSCs). Hence, microRNA (miRNA) expression profiles of primary MB samples were compared to CD133+ NSCs, aiming to identify deregulated miRNAs involved in MB pathogenesis. Expression profiling of 662 miRNAs in primary MB specimens, MB cell lines, and human CD133+ NSCs and CD133- neural progenitor cells was performed by qRT-PCR. Clustering analysis identified two distinct sub-types of MB primary specimens, reminiscent of sub-types obtained from their mRNA profiles. 21 significantly up-regulated and 12 significantly down-regulated miRNAs were identified in MB primary specimens relative to CD133+ NSCs (p<0.01). The majority of up-regulated miRNAs mapped to chromosomal regions 14q32 and 17q. Integration of the predicted targets of deregulated miRNAs with mRNA expression data from the same specimens revealed enrichment of pathways regulating neuronal migration, nervous system development and cell proliferation. Transient over-expression of a down-regulated miRNA, miR-935, resulted in significant down-regulation of three of the seven predicted miR-935 target genes at the mRNA level in a MB cell line, confirming the validity of this approach. This study represents the first integrated analysis of MB miRNA and mRNA expression profiles and is the first to compare MB miRNA expression profiles to those of CD133+ NSCs. We identified several differentially expressed miRNAs that potentially target networks of genes and signaling pathways that may be involved in the transformation of normal NSCs to brain tumor stem cells. Based on this integrative approach, our data provide an important platform for future investigations aimed at characterizing the role of specific miRNAs in MB pathogenesis.

Project description:UnlabelledCell secretion is an important mechanism for stem cell-based therapeutic angiogenesis, along with cell differentiation to vascular endothelial cells or smooth muscle cells. Cell-released microvesicles (MVs) have been recently implicated to play an essential role in intercellular communication. The purpose of this study was to explore the potential effects of stem cell-released MVs in proangiogenic therapy. We observed for the first time that MVs were released from adipose-derived stem cells (ASCs) and were able to increase the migration and tube formation of human umbilical vein endothelial cells (HUVECs). Endothelial differentiation medium (EDM) preconditioning of ASCs upregulated the release of MVs and enhanced the angiogenic effect of the released MVs in vitro. RNA analysis revealed that microRNA was enriched in ASC-released MVs and that the level of microRNA-31 (miR-31) in MVs was notably elevated upon EDM-preconditioning of MV-donor ASCs. Further studies exhibited that miR-31 in MVs contributed to the migration and tube formation of HUVECs, microvessel outgrowth of mouse aortic rings, and vascular formation of mouse Matrigel plugs. Moreover, factor-inhibiting HIF-1, an antiangiogenic gene, was identified as the target of miR-31 in HUVECs. Our findings provide the first evidence that MVs from ASCs, particularly from EDM-preconditioned ASCs, promote angiogenesis and the delivery of miR-31 may contribute the proangiogenic effect.SignificanceThis study provides the evidence that microvesicles (MVs) from adipose-derived stem cells (ASCs), particularly from endothelial differentiation medium (EDM)-preconditioned ASCs, promote angiogenesis. An underlying mechanism of the proangiogenesis may be the delivery of microRNA-31 via MVs from ASCs to vascular endothelial cells in which factor-inhibiting HIF-1 is targeted and suppressed. The study findings reveal the role of MVs in mediating ASC-induced angiogenesis and suggest a potential MV-based angiogenic therapy for ischemic diseases.

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MRNA and miRNA expression profile reveals the role of miR-31 overexpression in neural stem cell.

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mRNA and miRNA expression profile reveals the role of miR-31 overexpression in neural stem cell.

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